Neuropeptide Y (hereinafter referred to as NPY) is a peptide which consists of 36 amino acid residues and was isolated from porcine brain in 1982. NPY is widely distributed in the central nervous system and peripheral tissues of humans and animals.
It has been reported that NPY possesses a stimulating activity of food intake, an anti-seizure activity, a learning-promoting activity, an anti-anxiety activity, an anti-stress activity etc., in central nervous system, and it may be pivotally involved in the central nervous system diseases such as depression, Alzheimer's disease and Parkinson's disease. NPY is thought to be associated with the cardiovascular diseases, since it induces a contraction of smooth muscles such as blood vessels or cardiac muscles in the peripheral tissues. Furthermore, NPY is also known to be involved in the metabolic diseases such as obesity, diabetes, and hormone abnormalities (Trends in Pharmacological Sciences, Vol. 15, and 153 (1994)). Therefore, an NPY receptor antagonist is expected as a medicine for preventing or treating various diseases involved in the NPY receptor.
Subtypes of Y1, Y2, Y3, Y4, Y5, and Y6 have now been identified as the NPY receptor (Trends in Pharmacological Sciences, Vol. 18, and 372 (1997)). It has been suggested that the Y5 receptor is at least involved in the feeding behavior and its antagonist is expected as an anti-obestic agent (Peptides, Vol. 18, and 445 (1997)).
Quinazoline compounds having similar structures to those of the compounds of the present invention and exhibiting an NPY receptor antagonistic activity are described in WO97/20820, WO97/20821, WO97/20823 and the like. In addition, it is described that urea derivatives having a sulfonamide group and amide derivatives having a sulfonyl group in WO99/64349 and benzyl sulfonamide derivatives in EP1010691-A, have an NPY antagonistic activity.
Compounds having similar structures to those of the compounds of the present invention are described in JP59-16871-A and WO97/15567. Their activities are quite different from that of the present invention and these documents do not suggest the present invention.